Herpes simplex , varicella zoster

, Epstein Barr virus infection

Moderator : Dr. Anil Sajjan sir
Presenter : Dr. Y. Rohith
Herpes Simplex Infections
● Herpes simplex virus (HSV) belongs to alphaherpesvirinae.
● HSV-1 and HSV-2 belong to subfamily of alphaherpesvirinae.
● Eight herpes viruses are pathogenic to human, of which HSV-1 and HSV-2
are the major contributors.
● Approximately one-third of children from lower socioeconomic population and
about 20% from middle class have serologic evidence of HSV infection by 5
years of age.
ETIOLOGY
● HSV-1 primary infection usually occurs in infancy or childhood, whereas
primary infection with HSV-2 occurs after onset of sexual activity.
● Humans are the only known reservoir.
● The viral glycoproteins are the major target for humoral immunity whereas
other nonstructural proteins are important targets for cellular immunity.
● The glycoproteins like gB and gC mediate cellular attachment, gD is required
for viral entry, gE for efficient expression of late genes and gI is a potent Fc
receptor.
PATHOGENESIS
● All herpesviruses have characteristic property of becoming latent after primary
infection.
● Reactivation of HSV is regulated by the host immune factors.
● Recurrences are more common with HSV-1 causing orolabial infections and
and HSV-2 causing genital infections.
● Primary infection: occurs in individuals who have not been previously
infected by HSV-1 or HSV-2. The infections are severe due to lack of
seropositivity.

● Nonprimary infection: occurs in patients who have been exposed previously

to either HSV-1 or HSV-2. The infections are not severe due to some level of
cross protection.

● Recurrent infection: During primary or non-primary infection, HSV

establishes latent infection in regional sensory ganglion neurons. Usually they
are asymptomatic.
CLINICAL FEATURES
● Clinical manifestations depend on the type of infection, type of virus, port of entry.
● The typical lesions in primary infection manifest as small to large vesicles surrounded
by an erythematous base, which eventually develops into ulcers and usually heals
without scarring.
Cutaneous Herpes:
● Cutaneous herpes infections caused by direct contact and lesions develop at the port
of entry.
● The manifestations range from severe pain to burning and itching mainly before the
eruption of lesion.
● Herpetic whitlow refers to HSV infection of fingers and toes. Surgical intervention is
contraindicated.
● Orolabial Infection:
● Primary infection classically presents with extensive orolabial painful lesions ,
high fever, irritability, drooling of saliva, refusal to feed and tender
submandibular lymphadenopathy.
● Lesions heal without scarring in 6–10 days. Dehydration is the most common
indication for hospitalization
Genital Herpes (due to HSV-2):

Primary infection: Nonspecific symptoms develop within 7 days of incubation.

Lesions are distributed over the shaft of the penis in males and over labia, mons
pubis, cervix and vaginal mucosa in females. Tender lymphadenopathy appears in
2nd and 3rd week of infection.
Nonprimary Less severe lesions with more rapid healing and less severe
complications.
Reactivation Usually asymptomatic, the carriers keep shedding the virus for long
time.
Neonatal Herpes:
● The estimated prevalence of neonatal herpes is 1 in 3,000–5,000 live births.
● Around 70–80% neonatal HSV infections are due to HSV-2.
● The infection occurs more commonly in infants born to mother with recent
infection rather than due to recurrent genital herpes.
● HSV infection is acquired during in utero, peripartum or postpartum, often
during delivery.
● Patterns of Neonatal Herpes
● Neonatal HSV infection manifests in three ways with almost equal proportions
having considerable clinical overlap:
● (1) Skin, eye and mouth (SEM) form is never asymptomatic. They present
with skin lesions from birth or typically manifests within 2 weeks of life,Usually
the skin lesions appear at the site of trauma as vesicles..The common ocular
lesion is keratoconjunctivitis which can progress to chorioretinitis, cataract
and retinal detachment
● (2) Central nervous system (CNS) infection with or without skin lesions can
present as seizures lethargy and irritability
● (3) Disseminated form presents as shock, hepatomegaly, jaundice, bleeding
and respiratory distress within 5–11 days of life. Nearly 70% of cases
demonstrate skin lesion during the illness which are often absent at the onset
of symptoms.
DIAGNOSIS
● Cytopathological effects of HSV and isolation on viral culture are the gold
standard for diagnosing herpes infection.
● Fluorescent antibody staining and enzyme immunoassay are used for culture
confirmation.
● Isolation of virus or viral DNA by PCR is diagnostic method of choice.
● Histological examination and viral culture of brain tissue specimen are the
most definitive method of confirming the diagnosis of encephalitis.
● Bedside investigation like Tzanck smear can be used to demonstrate the
multinucleated giant cell.
Treatment
● No treatment is generally required except in primary infection, severe
recurrent infection, or in immunocompromised patients are treated with oral
acyclovir for 5-7 days.
Varicella
● Varicella (chickenpox) is a highly infectious disease caused by primary
infection of VZV.
● The illness is characterized by an exanthematous vesicular rash with a
centripetal distribution.
● The rash typically begins as maculopapular lesion on first day of fever.
● The course is usually benign and lasts for about 7 days.
● VZV can remain latent and activate years later as herpes zoster (shingles).
EPIDEMIOLOGY
● The virus infects only primates and man is the only reservoir.
● All age groups can be infected with predisposition for younger ages.
● The disease usually occurs during hot temperate climate season.
● Immunocompromised patients, infants and adults are more prone to develop
serious disease.
TRANSMISSION
● Varicella virus is transmitted from a patient to others mainly by direct contact
from skin lesions.
● The airborne route also contributes to VZV spread as VZV has been detected
by PCR in nasopharynx of children during pre-eruptive stages of the infection.
● Crusts from chickenpox lesions do not contain live virus. Infectivity is
maximum during prodromal period and decreases when eruptions become
crusted.
● Period of infectivity ranges from 48 hours prior and up to 3–7 days after the
rash appears.
ETIOPATHOGENESIS
● Chickenpox is caused by the varicella zoster virus , a DNA virus of the herpes
virus family.
● The virus is present in respiratory secretions and the skin lesions of an
affected child and is transmitted either by air-borne spread or through direct
contact.
● The portal of entry is the respiratory tract.
● During the incubation period of 10-21 days, the virus replicates in the
respiratory mucosa followed by viremic dissemination to skin and various
organs.
● During the latter part of the incubation period, the virus is transported to the
respiratory mucosa and leads to infectivity even prior to appearance of the
rash.
● The period of infectivity lasts from 24-48 hours before the rash until all the
vesicles are crusted.
● The disease is highly contagious with secondary attack rates of 80% among
household contacts.
● VZV establishes lifelong latent infection in the sensory ganglia.
● Reactivation, especially during depressed immunity, leads to herpes zoster.
Clinical Features
● The prodromal period is short with mild to moderate fever, malaise, headache
and anorexia.
● The rash appears 24-48 hours after the prodromal symptoms as intensely
pruritic erythematous macules first on the trunk.
● The rash rapidly spreads to the face and extremities while it evolves into
papules, clear fluid-filled vesicles clouded vesicles and then crusted vesicles.
● Several crops of lesions appear and simultaneous presence of skin lesions in
varying stages of evolution is a characteristic of varicella.
● The rash lasts 3 to 7 days and leaves behind hypopigmented or
hyperpigmented macules that persist for days to weeks.
Complications
● Secondary bacterial infections of the skin lesions may occasionally result in
necrotizing fasciitis usual organisms are S. aureus and S. pyogenes.
● Neurologic complications include meningoencephalitis, acute cerebellar
ataxia, transverse myelitis and optic neuritis.
● The progressive varicella syndrome is a complication of chickenpox in the
immunocompromised, neonates, pregnant women and sometimes even
healthy children, adolescents and adults.
● This is characterized by continued development of lesions, hemorrhagic
lesions, coagulopathy and visceral organ involvement including hepatitis,
pneumonia and encephalitis.
Chickenpox in pregnancy :
● Congenital varicella syndrome may occur following infection in the first and
second trimester at a frequency of 0.4-2%
● It is characterized by skin scarring, malformed extremities, cataracts and brain
abnormalities..
● If the disease occurs in the mother 5 days before and 2 days after delivery,
severe and often fatal neonatal disease may result.
Diagnosis
● The diagnosis is clinical and usually not difficult. Chickenpox should be
differentiated from other vesicular exanthem such as herpes simplex,
enteroviral infections (hand-foot-and-mouth disease), insect bites
● In atypical cases, the diagnosis is made on Tzanck smear of the lesions
(showing multinucleated cells) and demonstration of anti-IgM antibodies to
varicella.
Treatment
● Management is symptomatic and includes antipyretics, antipruritic agents and
good hygiene.
● The child should not attend school until no new lesions appear and all lesions
have crusted.
● Administration of oral acyclovir within 24 hours of onset of rash in healthy
children reduces the duration of rash by one day and lesions by 25%
● IV acyclovir is recommended for patients with complicated varicella and
illness of any severity in high-risk patients such as neonates and
immunocompromised children.
Varicella vaccine
● Two doses are recommended to reduce the risk of breakthrough infections
with waning immunity. Internationally available monovalent preparation
(Varilrix; and Variped) and its combination with MMR (MMR-V, Priorix-Tetra)
● MMR-V is associated with higher rate of adverse events (fever, rash,
seizures) in patients 12-23 months old than MMR and varicella administered
separately.
● 0.5 ml , subcutaneously given , All children, especially high-risk categories
Two doses >3 months apart; preferably at 15-18 months (minimum 12
months) and 4-6 years.
Infectious Mononucleosis
● The EBV virus, a DNA virus of the herpes virus family, is shed in oral
secretions and transmitted
● The virus replicates in the oral epithelial cells then spreads to salivary glands
travels in the B lymphocytes in the blood to the lymphoreticular system
including lymph nodes, liver and spleen.
● The CD8 lymphocytes proliferate to check this replication of virus in the B
lymphocytes and represent the atypical lymphocytes seen in EBV infection.
Clinical Features
● Symptomatic EBV infections in older children and adults are characterized by
insidious onset with symptoms such as malaise, fatigue, fever, headache,
nausea, sore throat, abdominal pain and myalgia.
● Examination shows pharyngeal inflammation with exudates and petechiae at
the junction of soft and hard palate.

● Generalised lymphadenopathy ,mild splenomegaly (50%) and hepatomegaly

(10%). Maculopapular rashes are seen in 3-15% and in 30% of those who
have received ampicillin or amoxicillin.
Complications

● Complications are rare and include splenic rupture following minor trauma
● Airway obstruction due to enlargement of oro pharyngeal lymphoid tissues,
meningitis, seizures, ataxia, myocarditis , haemolytic anemia,
thrombocytopenia, neutropenia, aplastic anemia , interstitial pneumonitis and
pancreatitis.
Diagnosis
● Most patients show leukocytosis and absolute lymphocytosis, with presence
of atypical lymphocytes.
● The hepatic transaminases elevated in 50% patients.
● The Paul-Bunnell test (heterophile antibody test) is used for screening.
● IgM antibody to viral capsid antigen (lgM VCA) is confirmatory for diagnosing
acute infection.
Treatment
● Rest and symptomatic therapy are mainstays of management.
● Treatment with prednisalone (1 mg/kg/ day for 7 days) is advised for
complications such as hemolytic anemia, airway obstruction, meningitis and
thrombocytopenia with bleeding.
Other Manifestations of EBV Infections
● EBV has oncogenic potential and associated with aggressive proliferative
disorders such as virus associated hemophagocytic syndrome,
● Oral hairy leukoplakia and lymphoid interstitial pneumonitis patients with
AIDS,
● Nasopharyngeal carcinoma ,
● Burkitt lymphoma,
● Hodgkin disease.
● Tumours in immunocompromised patients.
Thank you